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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

Robert Kingsley of the Quadram Institute Bioscience in the United Kingdom will locate the typhoid fever-causing bacteria S. Typhi in water reservoirs in Harare, Zimbabwe, and identify any associated protozoa species present in the water that may be supporting disease spread. Typhoid fever is endemic in Zimbabwe, with several major outbreaks reported in the last decade. The bacteria persist in unclean aquatic environments, possibly supported by protozoa, and are transmitted to humans through ingestion of contaminated drinking water. They will detect S. Typhi in sewage effluent and low-quality drinking water in hotspots of typhoid transmission by enrichment culture and PCR, and use whole genome sequencing to establish the phylogenetic relationship between these bacteria and clinical typhoid isolates in the same city. They will also amplify 18S rDNA from the sewage and drinking water samples to characterize the microbial community in water and define the protozoa population. These data will help identify potential synergistic interactions between S. Typhi and other microbes to inform prevention strategies.

France Daigle of the University of Montreal in Canada will identify the microorganisms that enable the survival of the typhoid fever-causing bacterium, Salmonella enterica serovar Typhi, at low levels in water, and thereby enhances disease spread. Typhoid fever spreads through contaminated food and water, and results in over 125,000 deaths annually worldwide. S. Typhi are so-called auxotrophic bacteria because they rely on an external source of the essential amino acids that they need to grow. Microbial interactions may provide nutrients and also increase bacterial fitness and support persistence by protecting them from the environment, thereby increasing the rate of disease transmission. They will assemble a microbial community in water consisting of three components: one protozoan (from a group known to promote bacterial survival); a defined consortium of bacteria representative of the human fecal microbiota; and fluorescently-tagged S. Typhi. They will evaluate the ability of S. Typhi to grow in these microcosms, and how they grow, such as in biofilms or inside the protozoa. They will also determine whether these persistent S. Typhi are better able to infect and survive in human cells. Finally, water samples from an endemic region in East Africa will be analyzed for the presence of S. Typhi and identified beneficial microbial partners using quantitative PCR.

Denise Monack of Stanford University in the U.S. will use a genetic approach to identify the molecular mechanisms that enable the typhoid fever-causing bacterium S. Typhi to survive in aquatic environments and to rapidly adapt to transmission to humans. Annually, S. Typhi causes over 20 million infections and 200,000 deaths, mostly among populations that lack access to clean drinking water. Understanding how S. Typhi persists in water and then quickly adapts to its human host is critical for controlling transmission. Bacteria use various mechanisms to adapt to environmental changes, including so-called RNA thermometers (RNATs), which form secondary structures in mRNAs that can rapidly activate gene expression when temperatures change. They will use their established genetic screening approach to identify new RNATs in S. Typhi and validate their ability to promote bacterial persistence within aquatic microbial communities by generating mutants. They will also follow up on past work in which a bioinformatics approach identified new RNATs that may regulate the expression of the chitinase enzyme, which is used by the cholera-causing bacterium to bind to plankton and create a protective environmental niche. They will evaluate whether chitin is also important for S. Typhi persistence and transmission.

Windy Tanner, formerly at the University of Utah and now at Yale University in the U.S., together with Jim VanDerslice of the University of Utah and colleagues from Mehran University of Engineering and Technology in Pakistan, will analyze water samples to determine the conditions that promote the survival of the typhoid fever causing bacterium Salmonella Typhi, and they will use metagenomic deconvolution to identify any gene exchange from other microbial species that may produce drug-resistant strains. S. Typhi is responsible for over 100,000 deaths each year, mostly in the developing world where fecal contamination of food and drinking water is common. The emergence of drug-resistant strains has limited the available treatment options. Biofilms are environmental niches with complex microbial communities and are ubiquitous in the environments where S. Typhi is commonly found. They will sample water and biofilms from a variety of these environments along the fecal-drinking water transmission route in the Sindh province of Pakistan and test for the presence of S. Typhi using qPCR and culture methods. They will also evaluate whether specific organisms stabilize and protect S. Typhi in these biofilms and could cause resistance gene exchange.

Juliana Cassataro of the Universidad Nacional de San Martín-CONICET in Argentina will test whether the bacterial protease inhibitor Omp19 can make vaccines more effective when they are administered orally. Oral delivery of vaccines is far simpler than by injection, which is particularly useful in low-resource settings, and it may also stimulate mucosal immunity making them more effective against some diseases. However, most vaccines administered orally are degraded in the stomach or do not induce a sufficient immune response to protect against the disease. In Phase I, while at the Universidad de Buenos Aires-CONICET, they discovered that Omp19 protects antigens from degradation and serves as an adjuvant, contributing to induction of both a mucosal and systemic immune response in mice orally immunized with proteins from the Salmonella bacterium and the Toxoplasma parasite, both of which have mucosal routes of infection. In Phase II, they will extend their mechanistic studies in order to move towards a Phase I clinical trial, and evaluate the ability of Omp19 to help induce an immune response in mice upon oral vaccination against Enterotoxigenic E. coli (ETEC), which is the most common cause of bacterial diarrhea in children from developing countries.

Hope Neighbor of Camber Collective in the U.S. will use applied behavioral research to better understand how and why young, sexually active women who are approaching marriage in West Africa make decisions on family planning products. Women appear to regulate their fertility differently based on their specific situation and needs. Young women who are not yet married tend to use unsafe or ineffective practices such as herbal remedies and abortion. They will recruit women in this group to fill out journals to generate evidence on the nature of their fertility planning needs and identify specific attributes of contraceptives that would fit better into their daily lives. They will also develop hypothetical prototype contraceptives by involving the participants in a card game to identify ways of modifying existing contraceptives, such as enabling over-the-counter availability, and key attributes for future contraceptives that better suit their needs.

Kelly JohnstonLiverpool School of Tropical MedicineLiverpool, United Kingdom

Grand Challenges Explorations

Neglected Tropical Diseases

8 Oct 2013

Kelly Johnston and others from the Liverpool School of Tropical Medicine in the United Kingdom will develop a cell line from a parasitic filarial nematode worm that can proliferate continuously in vitro to enable high-throughput screening of candidate anti-filarial drugs. Current drug screening efforts are limited by the complex life cycle of the worms and the difficulties of obtaining sufficient numbers of worms. They will isolate worm cells from various life cycle stages and use a high-content screening approach to monitor thousands of cells cultured under different conditions to increase the probability of detecting a stably growing cell line. Once one or more stable cell lines have been produced, they will establish optimal culture conditions for drug screening assays.

L. David SibleyWashington University in St. LouisSt. Louis, Missouri, United States

Grand Challenges Explorations

Human and Animal Health

10 Oct 2013

L. David Sibley at Washington University in St. Louis in the U.S. is developing a long-term in vitro intestinal epithelial culture system for the intracellular parasite Cryptosporidium, which causes severe diarrheal disease in both humans and animals, and is refractory to many anti-parasitic drugs. Currently, Cryptosporidium can only be grown in infected calves or in short-term in vitro cultures, which cannot be used for the high-throughput chemical screens needed to identify new drugs. In Phase I, they optimized the in vitro culture of isolated intestinal stem cells from human and mouse biopsies, and identified factors to control their differentiation into primary epithelial monolayers, which can better support the growth of intestinal pathogens. This led to around a five-fold increase in the rate of asexual replication of Cryptosporidium, which was enough to successfully test a chemical growth inhibitor. In Phase II, they will further improve culture conditions to support longer-term in vitro growth of Cryptosporidium, which will then be tested for stability and infectivity. They will also develop antibodies against specific developmental stages to help identify culture conditions that enable the parasite to undergo a complete life cycle, which will be valuable for culturing and screening efforts.

Edwin Routledge of Brunel University in the United Kingdom will work towards developing an artificial snail decoy to attract the parasite Schistosoma mansoni, which causes chronic disease. The parasites first develop inside aquatic snails, which they locate via chemical cues (chemoattractants), before they can infect humans. Routledge will identify the relevant chemoattractants by isolating and fractionating chemicals from the snails, and test the ability of these chemicals to attract the parasites. Effective chemoattractants will be characterized and ultimately incorporated into a biodegradable matrix to generate an artificial snail that is easy to deploy in the field and can trap and destroy the parasites, thereby reducing human transmission.

Sara Grobbelaar of Stellenbosch University in South Africa will develop a platform that can analyze existing real-time data on the stocks of health products at clinics across South Africa and present it to all players in the supply chain to ensure products are available when needed. In partnership with a Northern academic institution they will collect and sort relevant data, analyze trends, and develop decision-making tools. The platform will allow analysis, modeling, and forecasting in the health product supply chain so that unexpected changes such as supply disruptions or epidemics can be accommodated.

Peter LillehojUniversity of California, Los AngelesLos Angeles, California, United States

Grand Challenges Explorations

Cell Phone Applications

1 Nov 2010

Peter Lillehoj and Chih-Ming Ho of the University of California, Los Angeles in the US. will develop a disposable malaria biosensor based on a SIM card platform. This SIM card-biosensor will allow malaria detection to be performed using a cell phone, making diagnostic testing more widely available in rural and decentralized settings.

Elijah Songok of the Kenya Medical Research Institute in Kenya will design and test a fortified school meal product with deworming properties for treating soil transmitted helminths (parasitic worms) among schoolchildren in developing countries. Schoolchildren are most at risk of infection-associated morbidities such as stunting and chronic dysentery. However, current mass drug administration strategies are associated with the development of drug resistance, and may not be sustainable long term. They will fortify cornflour with seed extracts of the tropical fruit, Carica papaya (pawpaw), which can significantly increase clearance of the parasite, and use it to make porridge, which is cheap and a common school meal snack in developing countries. They will test its efficacy in a randomized pilot study in six elementary schools in rural Kenya.

Ricardo Capúcio de Resende of Universidade Federal de Viçosa in Brazil will design and test a new machine to enable women smallholder farmers in sub-Saharan Africa to more efficiently and effectively plant seeds. He has designed a new seeder concept using only two rotating parts, which is light, easy to use and maintain, and can simultaneously plant two crops. He will query local manufacturers and users to further develop the design, and then produce prototypes that will be bench- and field-tested for manufacturability and performance. The results will be used to produce the final seeder design, and this design concept could be applied to other agricultural machines.

Niaina Rakotosamimanana of the Pasteur Institute of Madagascar in Madagascar will develop a low-cost tuberculosis diagnostic and molecular test for pregnant women using dried blood samples drawn from finger pricks. This dried-blood spot based test is minimally invasive, can be used in remote areas where people lack access to all-weather roads and lack of infrastructure that has direct impact on health outcomes. The dried-blood spot can be sent via mail to the health centers for testing without established cold chain methods and meets several of the criteria set by the World Health Organization regarding quality of TB diagnostic tools. Dried-blood samples have a wide range of diagnostic capacity and have been shown to have advantages over other biological samples in terms of cost, ease of collection, transport, and storage.

Our proposal will provide this life-saving treatment to isolated, extremely resource poor people by obviating the need for electricity. This will be achieved by applying recently developed hydrological engineering approaches to extract the pressure differential required for the adsorption process exploited by Oxygen concentrators. This project aims to develop and test an electricity free Oxygen concentrator suitable for a developing world health facility. This represents a major paradigm shift, as to-date the problem has been interpreted as how to supply electricity to an Oxygen concentrator. In comparison with solar and generator based approaches the prototype will require significantly less capital cost and maintenance. Further, construction out of locally available components will empower the community to independently and sustainably access this life-saving treatment.

Ahmad Khalil of Boston University in the U.S. will develop a low-cost bioreactor platform to simultaneously optimize growth conditions of multiple bacterial species for large scale production of biotherapeutics. The human gut microbiome plays an essential role in health and development and living microbial biotherapeutics could be an effective treatment in the case of damage by illness or malnutrition. Commercial production is limited by the capacity of bioreactors, which are costly and challenging to scale and relatively inflexible. Using their eVOLVER continuous culture system, which is modular, inexpensive, and highly scalable, they will adapt the set-up and optimize protocols to allow for the management of unique growth conditions for individual species in parallel, and dynamic mixing of cultures from individual pools to precisely tune multi-species formulations. They will conduct full-scale tests to evaluate their approach for optimizing production of human gut microbiota.

Sang-Yeon ChoNew Mexico State UniversityLas Cruces, New Mexico, United States

Grand Challenges Explorations

Diagnostics

1 May 2010

Sang-Yeon Cho and Immo Hansen of New Mexico State University in the U.S. seeks to develop a malaria test that measures antibody-antigen reactions through a nanohole to indicate the presence of malaria parasites.

Pietro Alano of the Instituto Superiore de Sanità in Italy will develop a biochip that mimics the midgut of the Anopheles mosquito and can be used to more easily and quickly test candidate anti-malarial compounds for blocking transmission of the causative Plasmodium parasite. Malaria is a potentially fatal infection caused by parasites transmitted between humans through the bites of infected mosquitoes. When a mosquito bites an infected person, immature Plasmodium gametocytes enter the mosquito and transform into an invasive ookinete stage in its midgut. They then traverse the gut wall to the external gut lumen, where they enter their parasite stage. To eliminate malaria, compounds are needed that block the transmission of Plasmodium. However, current methods to evaluate the candidate transmission-blocking drugs or vaccines that are under development are slow and involve feeding malaria-infected blood to mosquitoes, which is potentially dangerous. As an alternative, they will create a biochip to reproduce the mosquito midgut environment that can support the development of parasites, and develop a bioluminescent antibody-based technique to count successfully traversing ookinetes. They will test the performance of the biochip using known anti-transmission drugs.

Jacob McKnight and Mike Wilson of the University of Oxford in the United Kingdom will develop a simple application that contains information about the quality, location, and the nature and cost of services provided by the different pathology laboratories in Kenya so that doctors and patients can choose the one that best suits their needs. They will conduct surveys to collect key information on the pathology laboratories in the Nairobi area, and consult with doctors and medical associations to find out how they use those laboratory services and what needs to be improved. They will build the application using these data and in collaboration with users. Ultimately, the system should also help to improve the overall quality of services.

Amit Srivastava of Children's Hospital, Boston in the U.S., along with colleagues at MIT, will develop a novel drug compliance platform combining the use of mobile phones for a simple diagnostic test, with economic incentives. The device will include a platform that measures drug metabolites in bodily fluids to generate a readout. Test results submitted on time will result in immediate economic rewards, such as additional cell phone minutes.

Daniel SteinUniversity of MarylandCollege Park, Maryland, United States

Grand Challenges Explorations

Infectious Diseases

1 Nov 2010

Daniel Stein and Phillip DeShong of the University of Maryland in the U.S. will construct and test a vaccine platform that utilizes low-cost, stable surfactant vesicles to deliver antigens for a sustained mucosal immune response. If successful, the platform could be used to develop low-cost vaccines for bacterial infections where carbohydrates form the basis of protective immunity, such as bacterial pneumonia and diarrheal diseases.

Dr. Yoshihiro Kawaoka of the University of Tokyo in Japan will develop broadly effective influenza vaccines by mixing together epitopes of conserved fragments of the viral hemagglutinin (HA) protein, which only elicit a weak immune response, together with millions of different, non-naturally occurring fragments that elicit a strong immune response, to induce broadly cross-reacting antibodies. Influenza is of world-wide concern severely impacting public health and the global economy. Tens of millions of reported cases result in tens of thousands of deaths annually in the U.S. alone, and the rapid spread of the virus between countries causes epidemic or pandemic outbreaks. Traditional vaccines are directed towards selected epitopes in the head region of the viral HA protein because they elicit a strong immune response. However, these regions are frequently mutated, rendering the vaccines useless. Vaccines directed towards more conserved epitopes only elicit a weak immune response, but this can be strengthened using HA proteins previously unseen by the immune system. They will produce a library of millions of HA epitopes that contain artificial mutations in the immune-dominant regions while preserving the conserved regions. This should focus the production of highly reactive antibodies against the conserved HA epitopes, which will eliminate a wider range of influenza strains. They will test this using single and repeat immunizations of different mixes in ferrets. Once optimized, the vaccination strategy will be tested in ferrets pre-exposed to influenza virus to mimic the human situation. The result will be a single vaccination that protects against a wider range of influenza strains than traditional vaccines.

Samuel Okurut and a team from the National Agricultural Research Organization in Uganda will develop a simple low-cost tool for women smallholder farmers to more easily and efficiently harvest cassava, which is a major staple food in the developing world. The classical, manual method for harvesting cassava is labor and cost intensive, involving hoeing and digging in a bent posture. The new tool will be developed with input from women farmers and key stakeholders, and designed to be operated in a more upright posture. The cost-benefit of the tool will be tested in the field, and the feasibility of training and local fabrication will be explored.

Miguel Prudencio of Instituto de Medicina Molecular in Portugal will test the theory that modified live rodent malaria parasites (P. berghei) can be used in a vaccine to elicit a strong immune response in humans without being able to infect human red blood cells and cause illness. This was successfully tested in Phase I, and they also established that the human antigens carried by the parasites could induce a selective immune response in mice. In Phase II, they will test their vaccine in Phase I/IIa human trials and evaluate it for safety, tolerability, and immunogenicity. They will also extend their approach to another human malaria parasite P. vivax, and begin optimizing methods for large-scale vaccine production.

Chakib Tadj of École de Technologie Supérieure in Canada will design a non-invasive diagnostic tool using computer acoustical analysis of newborn cries to detect serious medical conditions such as heart defects and infections. Cry production in newborns can be influenced by neurological and physiological states. In this project's Phase I, Tadj and his team analyzed cries from 120 healthy and sick newborns to identify acoustic features that can be used for diagnostic purposes. In Phase II, they will build on these results by incorporating an additional 1000 infants, and expanding to other serious pathological conditions afflicting newborns. They will also develop a software-based diagnostic tool that can interpret recorded cries to help neonatologists detect specific pathologies affecting newborns.

Maria RodriguezOregon Health and Science UniversityPortland, Oregon, United States

Grand Challenges for Development

Saving Lives at Birth

1 Jan 2013

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in low-income countries. The majority of these deaths occur outside the health care system, and so an intervention that could be used in any setting and with minimal training could save lives. We will use an animal model to demonstrate appropriate uterine fill, and a proof-of-concept study to show stoppage of post-delivery bleeding and test ease of removal. Standard care for treating PPH consists of massage, uterotonics, and tamponade (i.e., "holding pressure"). Devices used to treat PPH via tamponade are not easily adaptable to low-resource settings with diverse climates and providers. A novel agent, the XSTAT mini sponge dressing, has proven successful in the acute cessation of traumatic non-compressible bleeding analogous to PPH. This device utilizes pre-packaged, environmentally stable, compressed medical sponges soaked with a hemostatic agent and administered by a light-weight applicator. The sponges, once deployed, exert uniform pressure to address multiple sources of bleeding and are easily removable.

Renjie Chang of Lavax in the U.S. will develop and test a vaginal suppository that uses a strain of commensal bacteria which has the ability to immobilize sperm and capture viruses. If successful, the bacteria could be used as a reversible contraceptive that also affords protection against viruses such as HIV and herpes.

Robert AitkenUniversity of NewcastleCallaghan, New South Wales, Australia

Grand Challenges Explorations

Contraceptive Technologies

1 May 2010

John Aitken of the University of Newcastle in Australia will study the mechanisms by which organic compounds called quinones may provide simultaneous protection against pregnancy and sexually transmitted disease. Aitken will test the capability of quinones to react to enzymes in semen and not only immobilize sperm, but also disrupt the infective nature of pathogenic microbes found in STD infections such as Chlamydia

Giulietta Saletti of the International Vaccine Institute in the Republic of Korea will work to develop an assay test that binds to tissue-specific cell markers to not only measure the concentration of anti-body secreting cells, but also identify which of those cells are targeted to mucosal tissues. If successful, this simple test that requires a small blood sample can be used in low-resource settings to measure mucosal immune responses to vaccines in infants and children.

Jasper Ogwal-Okeng of Makerere University in Uganda will test whether the insect-eating plants can reduce the population of mosquitoes and their larvae. Ogwal- Okeng will study optimal numbers and placement of such plants and record subsequent impact on mosquito and larvae populations to further refine this vector control method.

Randall Peterson of the University of Utah in the U.S. will develop a zebrafish model for high-throughput screens to identify compounds that inhibit the formation of gametes, i.e., sperm or eggs, (gametogenesis), which could lead to male and female contraceptives that last for weeks or months after only a single dose. They will generate transgenic zebrafish lines that express a selection of four fluorescently-labeled markers for different stages of gametogenesis that can be rapidly quantified to measure the effects of candidate compounds on blocking gamete production. The suitability of these zebrafish lines for high-throughput multi-well compound screens will be tested using known inhibitors of gametogenesis.

Joao Guilherme Bezerra Alves from the Instituto de Medicina Integral Professor Fernando Figueira in Brazil will perform a randomized controlled trial to assess whether a daily oral supplement of magnesium citrate can prevent placental vascular disease, which can lead to preterm birth. Placental vascular disease restricts the flow of nutrients to the fetus and can cause growth restriction and maternal hypertensive disorders. Magnesium is known to promote placental vascular flow, and magnesium citrate is safe, inexpensive and easily absorbed in the body. They will perform a clinical trial in two large hospitals in Brazil in which 3,000 pregnant women will be offered a daily magnesium supplement or a placebo control starting from up to 20 weeks of gestation and continuing until birth. The effect on various outcomes including placental function, preterm labor, and mother and child health will be evaluated.

George Warimwe of the Jenner Institute at the University of Oxford in the United Kingdom will develop a vaccine to protect a variety of species, including humans, sheep and cattle, against Rift Valley fever, which can cause serious illness. Current vaccines that are in development have safety concerns for use in humans. They have developed a Rift Valley fever vaccine using a replication-deficient simian adenovirus as a safe vector that is easy and inexpensive to manufacture, and have tested its safety and immunogenicity in mice, and begun field-testing in sheep in Kenya. They will test safety and immunogenicity of the vaccine and the effect of an adjuvant in calves and goats, and compare this with the data from mice and sheep.

Feng Qian of Tsinghua University in China will work to develop an inhaled drug particle using a scalable formulation process to deliver tuberculosis drugs directly into the lungs. They will develop micro-particles containing current TB drugs and will test their utility when inhaled.

Guozhi WangNational Institute for the Control of Pharmaceutical & Biological ProductsBeijing, China

Grand Challenges Explorations

Infectious Diseases

1 Nov 2010

Guozhi Wang of the National Institute for Control Pharmaceutical & Biological Products in China will assess the effectiveness of a new inexpensive skin test that can differentiate between true Tuberculosis infection and the markers of the BCG vaccination. Because the current TB screening protocol is not sensitive enough to tell the difference, this new test could lead to earlier and better treatment options for those with early-stage infections.

Kevin PlaxcoUniversity of California Santa BarbaraSanta Barbara, California, United States

Grand Challenges Explorations

Diagnostics

7 Apr 2010

Kevin Plaxco of the University of California, Santa Barbara, United States seeks to develop a diagnostics platform based upon measuring the electric current produced by the binding of antibodies to DNA molecules. If successful, this method will provide a rapid, single-step reagent free measurement of immune antibodies which could significantly augment disease detection and vaccine validation efforts.

Joseph TurnerLiverpool School of Tropical MedicineLiverpool, United Kingdom

Grand Challenges Explorations

Neglected Tropical Diseases

10 Apr 2013

Joseph Turner of the Liverpool School of Tropical Medicine in the United Kingdom will develop a small animal model of the parasitic disease onchocerciasis, also called river blindness, which is the second leading infectious cause of blindness. Treatment options for filarial infections are currently limited and lack effectiveness. Thus, small animal models of filarial infections are invaluable for preclinical testing of candidate drugs. In Phase I, they established the mouse model by infecting mice lacking an adaptive immune system with Onchocerca parasites isolated from infected cows, and tested its feasibility for screening drugs. In Phase II, they will expand their model, and use it for preclinically testing the safety and efficacy of several candidate drugs currently under development.

Warwick Grant of La Trobe University in Australia will develop a small animal parasite model to test candidate drugs for treating the parasitic nematode Onchocerca volvulus, which causes river blindness in humans. They will establish infection of the related parasite Cercopithifilaria johnstoni in rats and evaluate the pathology for similarity to the human disease. The model will then be validated for testing human anti-onchocercal drug candidates by analyzing the effect of drugs with proven success in patients. Once the model has been fully validated, they aim to perform routine assessments of candidate drugs.

Cheikh Tidiane Diagne of the Institut Pasteur de Dakar in Senegal will enable real-time remote sensing and monitoring of specimens during transport to laboratories in low-resource settings to facilitate diagnosis and assist researchers and health workers. Containing outbreaks during epidemics requires the early detection and rapid identification of pathogens, which means quickly and carefully collecting and transporting samples to laboratories. They will develop smart biosample preservation and transportation tools that can be monitored in real time with a remote digital interface. They will evaluate their platform for delivery of samples from several rural locations to a centralized laboratory.

David HughesPennsylvania State UniversityUniversity Park, Pennsylvania, United States

Grand Challenges

Annual Meeting Call-to-Action

23 May 2019

David Hughes of Pennsylvania State University, John Corbett of aWhere, and Rhiannan Price of DigitalGlobe, in the U.S. will develop a software platform comprising prediction algorithms that leverage artificial intelligence to predict where and when plant diseases and pests will occur from weather and satellite data to alert farmers to check their crops. Pests and diseases are moving targets, however most current surveillance methods monitor only their presence or absence. Predicting when and where they are likely to occur would be more valuable for preventing them. This has recently been made possible by studies on how environmental factors influence the emergence and behaviour of crop pests and diseases. They will use a systems approach that incorporates these new predictors along with historical data and couples them with an artificial intelligence component that learns from ground observations recorded using smartphones to improve accuracy. They will combine their existing agricultural intelligence platform and smartphone application with their prototype predictive model and test their approach with maize and cassava crops on farms across seven different counties in Kenya. The platform will produce location-specific forecasts that can be acted upon immediately by farmers.

Tobias Oker and a team from the National Agricultural Research Organization in Uganda will develop a simple plucking tool to more efficiently remove the pods from groundnuts, which is currently done by hand and is labor-intensive and time-consuming for women. They will query farming communities on current harvesting methods to refine their design, and evaluate performance, labor cost, and perceptions in the field using prototypes compared to traditional methods. They will also train users and local manufacturers to fabricate the tools and encourage their use.

Enterotoxigenic Escherichia coli (ETEC) cause diarrhea by producing two distinct enterotoxins that attack intestinal cells. Adrienne Paton and colleagues at the University of Adelaide in Australia propose to develop a harmless probiotic bacterium capable of binding and neutralizing both these enterotoxins by mimicking their respective receptors, thereby preventing disease.

Sumi Biswas of the Jenner Institute, University of Oxford in the United Kingdom will test three components from the mosquito's innate signaling pathways for possible use in a malaria vaccine. Biswas will test whether immunizing mammal hosts with these components can induce strong antibodies, which can be passed along to mosquitoes to enhance the insect's innate immune response, thus leading to the death of the malaria parasite in the vector.

Benson Wamalwa of the University of Nairobi in Kenya will develop and test a vaginal gel that contains zeolite nanoparticles which soak up the fructose present in semen. By “mopping” up the fructose, this gel will rob sperm of the energy needed for motility. If successful, the gel could be used as an inexpensive, non-hormonal contraceptive.

Tania Maria Ruffoni Ortiga from the Universidade Federal do Rio de Janeiro in Brazil will measure the levels of so-called ABC transporters throughout pregnancy, and during normal and preterm labor, and how they are influenced by infections such as malaria and influenza, to determine whether they might increase the risk of preterm labor. ABC transporters sit in the outer membranes of cells and actively transport drugs, toxins and immune signaling molecules out of them. In this way, they regulate the immune response, hormonal signaling and the activity of drugs such as antibiotics, which become particularly important during pregnancy and labor. They will collect human intrauterine tissue at different time points during pregnancy and during cesarean delivery from hospitals in Brazil and Canada, and investigate the distribution of ABC transporters and the association with infection. They will also use a mouse model of malaria to evaluate the effect on the levels and activity of the transporters.

Ashish Ganguly and colleagues from the CSIR-Institute of Microbial Technology in India will make an affordable paper-based diagnostic to quickly and precisely measure plasma gelsolin levels in expectant mothers to help predict premature delivery and postpartum recovery, thereby reducing new mother and child mortality rates. They will determine the value of plasma gelsolin levels for predicting postpartum-related problems using patient sampling and an animal model of preterm birth. They will also develop the diagnostic by identifying a plasma gelsolin binding peptide that will be used to coat an optimized paper strip, along with a cell phone based read-out to enable remote analysis by a centralized unit. This grant was selected through India's IKP Knowledge Park and their IKP-GCE program.

The project intends to identify challenges to accelerate linear growth among infants/children in low-income settings and strategies to overcome them. The study proposes delivery of an integrated package of interventions (nutritional, environmental, WASH and care) during pregnancy and early childhood in a community-based model. Using stratified randomization, the proposal has been designed in a manner that permits the assessment of the impact of these intervention packages when delivered synergistically or independently on the growth and development of the young child.

Balaji Teegala from BRUN Health Pvt. Ltd. in India will develop a Doppler stethoscope - Acousta - that acts both as a standard annular Y-shaped stethoscope and as a Doppler stethoscope. The problem in auscultating the fetal heart to identify birth asphyxia among other fetal morbidities is the difficulty, skill, and training needed while using a regular stethoscope. This is mitigated by active sensing systems like the fetal Doppler systems or cardiotocographs. However, these systems are burdensome to carry in addition to a stethoscope. Alternatively, electronic stethoscopes give clarity during auscultation but are predominantly targeted at specialties like cardiology, while still being passive systems in their approach to sensing physiology. Acousta is a combinatorial approach using both these systems.

Marnie WinterUniversity of South AustraliaAdelaide,, South Australia, Australia

Grand Challenges Explorations

Emerging Technologies

1 Nov 2019

Marnie Winter and Benjamin Thierry from the University of South Australia, together with Tina Bianco-Miotto, Claire Roberts, and Clare Whitehead of the University of Adelaide in Australia and the University of Toronto in Canada, will develop and test short-interfering RNAs (siRNA) high-density lipoprotein (HDL) nanocarriers for the treatment of preeclampsia. Globally, ten million women develop preeclampsia during pregnancy each year, which results in the deaths of 76,000 women and 500,000 babies; 99% of these are in developing countries. Most current treatments focus on treating the symptoms (high blood pressure and proteinuria) rather than the molecular causes. Some of the causative molecules, such as the angiogenesis inhibitor sFlt1, can be blocked by specific siRNAs, but the challenge is targeting the siRNAs to the right cells in the body. HDL delivery systems for this purpose are effective and safe, and both siRNAs and HDLs are stable at room temperature, important for therapies in resource-poor areas. They will optimize the formulation of their HDL nanocarrier manufacturing platform, and characterize siRNA loading, carrier stability, size, cellular uptake, and silencing ability in 2D culture. Further, they will bioengineer an ex-vivo placenta model that fully recapitulates the structural and phenotypic complexity of a preeclamptic placenta and use it to evaluate tissue penetration and silencing abilities of the siRNA-nanocarrier complex.

Maternal mortality ratios in Ghana referral hospitals remain as high as 957-1,004/100,000 live births. Poor outcomes and dismal quality of care stem from delayed identification of complications upon arrival; women wait can hours or even days for evaluation and treatment. Kybele-Ghana will implement its obstetric triage program to six referral hospitals over two years, ultimately reaching 80% of Ghana's tertiary hospitals.

Federico Costa of the Federal University of Bahia, Brazil, Mitermayer Galvão dos Reis of Fiocruz, Brazil, and Nathan Grubaugh and Albert I Ko of Yale University in the U.S. will establish metagenomic next generation sequencing in clinical settings in an urban region of Brazil classified as an infectious disease ‘hot spot’ to help develop new diagnostics and identify emerging pathogens. Rapid urbanization in Salvador, a metropolitan of 2.9 million inhabitants in Northeast Brazil, has produced a favorable environment for the emergence and spread of infectious diseases, and was the founding site for the recent Zika epidemic. Early detection is critical for preventing disease spread, particularly in Salvador, which is a transport hub and popular holiday destination. However, diagnosis can be challenging in low-resource settings, especially when the causative pathogen is unknown, the disease has diverse symptoms, or a known pathogen starts causing new symptoms. They will collect around 160 clinical samples from patients with suspected infections at a local infectious disease reference hospital and a maternity unit and apply a next generation sequencing approach together with the IDseq analysis platform to identify pathogens from the sequencing data.

Troy LeaderProgram for Appropriate Technology in Health (PATH)Seattle, Washington, United States

Grand Challenges for Development

Saving Lives at Birth

1 Mar 2019

Preeclampsia (PE) remains one of the leading global causes of maternal death and disability. Under this proposal, we seek to incorporate a new, innovative design feature to our prototype that will further improve its usability by enabling midstream urine collection and thus align the test process to that of a common one-step, at-home pregnancy test. No current PE diagnostic test, including the current protein-only dipstick, allows for such a simple test process.

Rozina Feroz AliInteractive Research and Development Global LimitedSingapore, Singapore

Grand Challenges Explorations

Immunization Demand

1 May 2019

Rozina Feroz Ali of Interactive Research and Development Global Limited in Singapore along with Subhash Chandir and Danya Arif will establish a subsidized carpool for Pakistani women in rural areas and urban slums to improve access to immunization centers and increase vaccination coverage. Poor vaccine coverage in Pakistan is a result of the combined effects of poverty, lack of education, poor access to transportation, and distantly located vaccination centers; populations in rural areas and urban slums are vulnerable to outbreaks of vaccine-preventable disease and an increased childhood mortality rate. They will develop a system to provide women with transport to vaccine centers at affordable rates, educate them on the importance of vaccination through short videos played during the ride, and promote the service in the community by branding the commuting vehicles with vaccine and schedule information. Dedicated vehicles will offer fixed-price, round trip transportation to vaccination centers along specific routes with designated pick-up and drop-off times. In addition to improving access to vaccination, this system will work to improve gender equality in Pakistan; the ability to travel independently decreases female dependence on male family members. They will test it in a rural setting or urban slum in Pakistan and evaluate the number of users, number of children vaccinated, and estimated impact on vaccine coverage.

Conor Walsh of Harvard University and Elisabeth Salisbury of the University of Massachusetts Medical School in the U.S. will develop a low-cost, wearable, monitoring device to improve kangaroo mother care for newborns in remote settings. Kangaroo mother care is an established childcare method that is particularly valuable for preterm infants. It uses clothing to attach the baby to the caregiver, thereby ensuring continuous skin-to-skin contact to provide warmth. However, too much or too little heat can also be dangerous, but there is currently no way to monitor that. They will develop and test washable, temperature- and stretch-sensitive materials that can attach to existing kangaroo mother care garments to monitor the temperature and breathing rate of the infant. The device will also be able to alert the parent using color or other simple cues when they need to warm or cool the infant or provide stimulation.

Fredos Okumu of the Ifakara Health Institute in Tanzania will develop technology to evaluate mosquito control interventions using a combination of artificial intelligence, infrared spectroscopy, and entomology. Malaria caused over 400,000 deaths in 2017, the majority in the developing world, and an effective way to control the disease is to target the mosquitoes that transmit it. Current tools cannot precisely measure mosquito age or life-expectancy, and are therefore unable to predict the impact of mosquito control interventions. The biochemical composition of the mosquito exoskeleton varies with species and age; as the types of chemical bonds change so does the amount of light absorbed in the mid-infrared region. This can be measured with mid-infrared spectroscopy (MIRS), and they will combine this with machine learning to measure the age of mosquito populations. Using a dataset collected from over 25,000 lab-raised mosquitoes, they have developed a supervised machine learning model that accurately predicts mosquito age and species. They will optimize this model to work also on wild mosquito populations, develop an online platform for real-time analysis of mosquito MIRS data, and test its ability to measure the effectiveness of malaria control interventions.

H.V. Jagadish of the University of Michigan in the U.S. will take disparate datasets on diverse topics, including education, health, and the environment, which are often reported using different geographical units such as Zip Code or County, and realign them to a common unit so they can be better compared and used. Jagadish will develop four general techniques for aligning data partitions and apply them to existing datasets in one state in the U.S. so that they can be viewed according to different geographical units. Jagadish will also produce an interface so that policy analysts and NGOs can easily access and query these data, and collect feedback to improve the approach.

Paul Dyson of Swansea University in the United Kingdom will work to control the incidence of sleeping sickness in humans, which is caused by the Trypanosome parasite transmitted by tsetse flies, by genetically modifying a fly gut bacterium to deliver double-stranded (ds) RNAs to block two important parasite proteins. Trypanosomes mature in the flies, thereby gaining the capacity to infect mammals. He will engineer the bacteria and introduce them into tsetse flies, then test the capacity of the dsRNAs to inhibit their target proteins in trypanosomes. This approach could lead to long-term control of this disease as the bacteria are maternally transmitted to the offspring.

Debra Weese-MayerAnn & Robert H Lurie Children's Hospital of ChicagoChicago, Illinois, United States

Grand Challenges Explorations

Wearable Sensors

1 Nov 2017

Debra E. Weese-Mayer, Roozbeh Ghaffari, John A. Rogers, Matt Glucksberg, Aaron Hamvas, Mark Fisher, Bill Grobman and Casey Rand of the Ann & Robert H. Lurie Children's Hospital of Chicago and the Center for Bio-Integrated Electronics at the Simpson & Querrey Institute, Northwestern University in the U.S. will develop a skin-like sensor for newborns that improves the value of kangaroo mother care (KMC), which is a method used to maintain skin contact with the mother to keep the baby warm. Kangaroo mother care is particularly useful for premature babies in low-resource settings, but it is difficult to monitor how often it is used once the mothers have gone home. They have developed a wearable, ultrathin sensor adapted to delicate newborn skin by fusing soft, stretchable bioelectronics that can measure multiple physiological parameters such as breathing rate and temperature non-invasively through the skin. The device also emits audio and visual alerts when potentially dangerous values are detected, and can store and transmit data wirelessly for clinical monitoring and analysis. They will adapt the sensor to also detect motion and develop it for use during kangaroo mother care. The device will be tested for usability on a panel of mothers and nurses in a clinic in South Africa, and for accuracy in a U.S. based medical center.

Eric LokerUniversity of New MexicoAlbuquerque, New Mexico, United States

Grand Challenges Explorations

Neglected Tropical Diseases

9 Oct 2013

Eric Loker of the University of New Mexico in the U.S., along with colleagues from KEMRI in Kenya, will test whether parasitic flatworms known as amphistome flukes can eradicate the human parasite Schistosoma with the goal of helping prevent human infections. These two types of worms co-inhabit the same snail species. The investigators will harvest large quantities of amphistome eggs from the rumens of routinely slaughtered goats and cattle, and use temperature and light to induce miracidia (larva) to hatch in the laboratory. These will then be tested for their ability to infect schistosome-transmitting snails and to block or prevent schistosome infections in these snails. This low-tech, low-cost approach is more environmentally friendly than current chemical approaches, and its application to transmission sites can be easily halted once infection rates are under control.

Jason Rasgon of the Johns Hopkins Bloomberg School of Public Health in the U.S. will engineer a virus to express a scorpion toxin that kills mosquitoes. After infecting mosquito larvae, the virus will express the killer gene when the insect becomes old enough to reproduce, but not old enough to transmit the malaria parasite. By allowing the mosquito to reproduce, the virus not only will be transmitted vertically to the next generation, but will also significantly slow the evolution of resistance to the gene.

Andrew Jackson of the University of Liverpool in the United Kingdom will develop a diagnostic tool for Animal African Trypanosomiasis (Nagana), which is caused by unicellular parasites known as trypanosomes and threatens up to 50 million cattle in sub-Saharan countries. To avoid immune detection, the causative trypanosomes change their DNA sequences (genomes), particularly in genes encoding for cell surface glycoproteins, which also affects the symptoms the parasites cause. They will sequence these trypanosome genes from forty parasites spanning diverse countries and hosts to quantify their variation. By associating the variation with disease factors, such as virulence and severity, this profile of variation can be developed as a diagnostic marker to improve disease management and treatment.

Floriano Silva of Fiocruz in Brazil will develop a drug screening assay using automated microscopy to test new drug candidates for toxicity towards adult helminth parasites, which cause a range of diseases. Current screening approaches cannot easily identify drugs that specifically target adult parasites, which is the most disease-relevant life cycle stage. He will develop and validate imaging and computational methods to automatically monitor physical characteristics of the parasites, and perform proof-of-principle drug screens using an FDA approved and an annotated compound library. This approach could be expanded to other parasites and used for screening larger drug libraries to identify new classes of drugs.

Aravind VijayaraghavanUniversity of ManchesterManchester, United Kingdom

Grand Challenges Explorations

Next Generation Condom

8 Oct 2013

Aravind Vijayaraghavan and a team from the University of Manchester in the United Kingdom propose to develop new elastic composite materials for condoms containing nanomaterials like graphene. This composite material will be tailored to enhance the natural sensation during intercourse while using a condom, which should encourage condom use.

Paul de FigueiredoTexas A&M University Health Science CenterCollege Station, Texas, United States

Grand Challenges Explorations

Microbial Biotherapeutics

1 May 2019

Paul de Figueiredo and Daniel Alge of Texas A&M University in the U.S. will develop a portable, disposable bioreactor for the low-cost production of gut microbial biotherapeutics at an estimated $0.09 per dose in low-resource settings. Dysfunction of the human gut microbiome is a common consequence of malnutrition in poor countries. It may be effectively treated with live biotherapeutics, yet current production methods are complicated and expensive. Glucose oxidase consumes oxygen as a co-substrate in glucose oxidation and has been shown to create hypoxic microenvironments in vitro, similar to that in the human gastrointestinal tract. They will engineer an inexpensive bioreactor by immobilizing glucose oxidase in a hydrogel placed in dialysis tubing and incubated in liquid media; the glucose oxidation reaction will deplete the bioreactor of oxygen and create an oxygen gradient to mimic the intestinal lumen. This will enable growth of a consortium of anaerobic bacteria, after which the microparticles will be removed by filtration. They will optimize the system using an artificial consortium of at least ten strains of common gut bacteria.

Gérrard Poinern of Murdoch University in Australia will develop and test an implantable subcutaneous device made from same calcium mineral that bones are made of, which will release contraceptive drugs in a sustained and controlled way for a period of months. Creating of this device uses ultrasound and microwave technology, allowing for eventual low-cost manufacture in developing countries.

Dilys WalkerUniversity of California San FranciscoSan Francisco, California, United States

Grand Challenges for Development

Saving Lives at Birth

1 Mar 2019

The innovation is “Virtual Mentor" that when triggered by a spoken command interacts audibly with the birth attendant during a postpartum hemorrhage (PPH) event to increase adherence to established management algorithms and timeliness of interventions. We will use an “off-the-shelf" package to rapidly and inexpensively develop the prototype for a PPH VM--the Amazon Alexa device.

Although intrauterine devices (IUDs) are effective long-acting contraceptives, IUD insertion is very complex, so IUDs are often unavailable in resource poor settings. Bioceptive's proposal is to create a reusable IUD inserter for the developing world with the goals that it is intuitive, Cu380A IUD compatible, safer, and low cost. Bioceptive will develop a reusable version of its patent-pending IUD inserter that makes the insertion procedure easier and safer, allowing more women worldwide to take advantage of one of the most effective forms of contraception. The design of this reusable inserter will be based on Bioceptive's disposable inserter, which is prohibitively expensive for use in the developing world. The reusable inserter will expand access to the most common type of intrauterine contraceptive device to millions of women at low cost. Bioceptive's IUD inserter will eliminate the need to use four separate instruments for IUD insertion, making the procedure simpler, safer and intuitive. Bioceptive's inserter replaces these other instruments with one intuitive device, allowing any healthcare worker to insert an IUD with minimal training, even in resource-poor settings. This will have a major impact on maternal health by addressing a major gap in access to IUDs, a most effective contraceptive option.

Owain Millington and Gail McConnell of University of Strathclyde in the United Kingdom seek to adapt existing imaging systems to provide non-invasive in vivo imaging of Leishmania parasites present in macrophages and dendritic cells, and then use a targeted laser to destroy them. They will also test the hypothesis that targeting these cells for destruction will stimulate protective immunity against future Leishmania parasite infections.

Jonah SachaOregon Health and Science UniversityPortland, Oregon, United States

Grand Challenges

Influenza Vaccine

20 Aug 2019

Jonah Sacha of the Oregon Health & Science University in the U.S. will explore a new approach to vaccine design by using a cytomegalovirus (CMV) vector expressing conserved influenza antigens to induce an effector memory T cell response that persists in the lungs and can provide lifelong immunity against influenza. The development of a universal influenza vaccine is a top global health priority: four pandemic outbreaks in the last 100 years killed tens of millions of people, and current antibody-mediated vaccines target highly variable antigenic proteins that are extremely strain-specific and unable to protect against future threats. Work on HIV and tuberculosis vaccines has shown that CMV-vectored vaccines can elicit and maintain effector memory T cells (TEM) at high frequency in the lung. While TEM don’t protect against infection, they restrict pathogen replication in the lung to the point that it is effectively eliminated. They will extend this work to influenza vaccine development, determining whether a CMV vaccine can protect cynomolgus macaque monkeys from the highly pathogenic 1918 influenza strain. After establishing the minimum lethal dose of the virus, they will vaccinate monkeys with a CMV vector expressing three highly conserved influenza viral proteins. They will characterize the subsequent cellular immune response, and then challenge the vaccinated animals with a low dose of 1918 influenza to evaluate the ability of the vaccine to protect them from infection.

Carmine Bozzi of Akeso Associates in the U.S., along with Maurice Masoda of Heal Africa in the Democratic Republic of Congo, will test the effect of treating hookworm infections in women smallholder farmers in the Democratic Republic of Congo on disease prevalence, iron status, and capacity for labor over a 12-month period. Hookworm infections are endemic in many regions, and infection rates can reach 50% of the population. Hookworms reside in the intestinal wall where they mediate blood loss causing iron deficiency and anemia, which is exacerbated in women due to menstrual blood loss and iron demands during pregnancy. This anemia in turn leads to reduced aerobic work capacity, therefore successful treatment of these infections could result in significant gains in labor productivity.

The project aims to discover molecular scaffolds that could be forerunners of EAEC therapeutics. Following a small molecule library screen, the team is evaluating hits, determining their mechanisms of action and their potential to be progressed as drug candidates. The group will also apply their anti-biofilm screen to other small libraries with a view to increasing the repertoire of promising leads against EAEC and other neglected enteric pathogens.

Nongnuj Tanphaichitr of the Ottawa Hospital Research Institute (formerly Ottawa Health Research Institute) in Canada will research whether the antimicrobial peptide LL-37 can be used simultaneously as a contraceptive and an anti-HIV treatment. LL-37 binds to specific sites on sperm which are thought not only to play key roles in egg fertilization but also interact with gp120 used by HIV to gain entry into cells.

Edward MitreThe Henry M. Jackson Foundation for the Advancement of Military MedicineBethesda, Maryland, United States

Grand Challenges Explorations

Neglected Tropical Diseases

9 Oct 2013

Edward Mitre and colleagues at the Henry M. Jackson Foundation for the Advancement of Military Medicine in the U.S. will develop a short course therapy for clearing adult filarial worms, which cause substantial morbidity and mortality, to enhance eradication efforts. Current antifilarial medications target only larval forms of the worms, requiring repeated administration until the natural death of the adults. Filarial infections are known to induce immune cells to release histamine, which can regulate the immune response. Using mouse models of filarial infections, they will evaluate whether a short course of standard antifilarial treatment combined with an antihistamine can clear adult worms and thereby more quickly cure the disease.

Kindie Tesfaye-Fantaye of the International Maize and Wheat Improvement Center in Mexico will develop a computational model that incorporates the variable characteristics of households and farms to better predict the outcomes of agricultural interventions in Ethiopia in order to inform policy choices. Agriculture is central to the Ethiopian economy; it accounts for almost 50% of the gross domestic product and 80% of total employment, yet the industry struggles with limited infrastructure and environmental challenges. Prioritization of agricultural policies has generally relied on analysis of past observations, which are static and tend to ignore variability. They will build and validate an agent-based model that uses current data to model future outcomes, and input biophysical (e.g., soil, climate) and socioeconomic (e.g., household characteristics, land use, access to market and financing) data. They will test their model by comparing five candidate policy options under consideration by the government in terms of impact, effectiveness, efficiency, and inclusiveness. Once established, the model will be scaled up for policy intervention in other Sub-Saharan countries including Tanzania and Nigeria.

Rajeev Shrestha and colleagues at Dhulikhel Hospital, Kathmandu University in Nepal will apply metagenomic, next generation sequencing technology to identify causative pathogens of fatal acute encephalitis to improve diagnosis and treatment. Acute encephalitis syndrome (AES) annually affects over 100,000 individuals in low- and middle-income countries, causing substantial morbidity and mortality. It is a diverse disease caused by over 100 different pathogens, including viruses and parasites, making accurate diagnosis difficult, even in high-resource settings. This hinders prevention and treatment efforts, even though several effective vaccines exist. To better characterize the pathogens causing AES, particularly treatable and emerging ones, they will apply metagenomic, next generation sequencing technology to 60 banked cerebral spinal fluid samples collected from fatal acute encephalitis cases in Nepal as part of a nationwide AES surveillance program that covered 189 hospitals. They will validate and refine their technique using previously validated samples.

Renato Soibelmann Procianoy from the Universidade Federal do Rio Grande do Sul in Brazil will analyze the association between bacterial populations in the vagina and gut of mothers in their third trimester and in the meconium of very preterm newborns, with risk of preterm delivery. It was previously assumed that microbes from the mother are first transferred to the fetus during delivery. However, it was recently shown that this could happen already in the uterus, triggering a possible immune response by the fetus that may lead to premature birth, which is a leading cause of infant morbidity and mortality. They will use 16S rRNA-based bacterial sequencing technology on around 600 samples to compare the types of bacteria present in preterm infants with that in healthy term infants in a neonatal unit in the Clinicas Hospital in Porto Alegre. They will also track the changes in bacterial composition in healthy and sick newborns during their hospital stay, to identify types of bacteria associated with specific diseases such as diarrhea. All samples will be stored in a repository for future case-controlled studies.

Data SantorinoMbarara University of Science and TechnologyMbarara, Uganda

Grand Challenges for Development

Saving Lives at Birth

16 Dec 2013

Effective resuscitation could reduce intrapartum related neonatal deaths by 30%, and deaths from prematurity by 10%, creating the potential to save 347,200 babies annually. However, one in five trained healthcare professionals (HCPs) fail to perform the resuscitation technique correctly, and those that do, often experience a rapid decline in proficiency. Our Augmented Infant Resuscitator's advanced training capabilities, instant feedback mechanism, and objective self-audit and retraining abilities will maximize and sustain gains from effective resuscitation. The AIR prototype provides instant feedback to users about effective ventilation. This is measured using inexpensive instrumentation that calculates ventilation rate, air volume and air pressure delivered by the bag-valve-mask (BVM) across the resuscitation face-mask. These parameters correlate with the four most common mistakes that result in ineffective resuscitation: 1) Failed seal at the face-mask interface resulting in failure to inflate the lungs; 2) Blocked airways; and 3) Wrong ventilation frequency 4) Insufficient/shallow lung inflation. Each of these mistakes can cause death or brain damage. AIR also records performance on an internal memory card for future feedback, improving HCPs training by identifying persistent gaps in technique.

Data SantorinoMbarara University of Science and TechnologyMbarara, Uganda

Grand Challenges for Development

Saving Lives at Birth

16 Dec 2013

Effective resuscitation could reduce intrapartum related neonatal deaths by 30%, and deaths from prematurity by 10%, creating the potential to save 347,200 babies annually. However, one in five trained healthcare professionals (HCPs) fail to perform the resuscitation technique correctly, and those that do, often experience a rapid decline in proficiency. Our Augmented Infant Resuscitator's advanced training capabilities, instant feedback mechanism, and objective self-audit and retraining abilities will maximize and sustain gains from effective resuscitation. The AIR prototype provides instant feedback to users about effective ventilation. This is measured using inexpensive instrumentation that calculates ventilation rate, air volume and air pressure delivered by the bag-valve-mask (BVM) across the resuscitation face-mask. These parameters correlate with the four most common mistakes that result in ineffective resuscitation: 1) Failed seal at the face-mask interface resulting in failure to inflate the lungs; 2) Blocked airways; and 3) Wrong ventilation frequency 4) Insufficient/shallow lung inflation. Each of these mistakes can cause death or brain damage. AIR also records performance on an internal memory card for future feedback, improving HCPs training by identifying persistent gaps in technique.

Michael Chan of the Ohio State Research Foundation in the U.S. will develop an engineered strain of bacteria used to ferment beans in traditional Asian and African diets, to display an antigen from the Tuberculosis bacterium. The engineered bacillus will then be used to make the traditional Asian dish natto, which can serve as a kind of oral vaccine to elicit a strong immune response. If successful, this strategy can be used to introduce a variety of disease antigens through culturally accepted foods.

Andrew EllingtonThe University of Texas at AustinAustin, Texas, United States

Grand Challenges Explorations

Diagnostics Systems

1 Nov 2017

Andrew Ellington of the University of Texas at Austin in the U.S. and the Alliance for Global Health will create stable enzymes that can be produced in developing countries and used directly in diagnostic assays to reduce costs. Enzymes are required in many diagnostic tests to detect pathogens such as malaria and HIV. However, they can be very expensive to buy and require refrigerated transport, making the tests prohibitively expensive in many developing countries where they are often most needed. Current enzymes, which are made by bacteria, can only be produced in sophisticated laboratories. They will adapt a novel, heat-stable enzyme to enable simple, on-site production for diagnostic tests at low cost and with minimal infrastructure. These features will facilitate accessibility and use in resource-poor conditions.

Sylvia van den Hurk and Sidney Hayes of the University of Saskatchewan in Canada proposes that bacteriophage lambda, a virus that invades bacterial cells and uses the host's genome to replicate, can be used as a vector to deliver DNA vaccines into targeted cells. Van den Hurk will test this lambda delivery platform its ability to induce long-term systemic and mucosal immune responses.

Marc Mitchell of D-tree International in the U.S. will develop an application that enables community health workers in Zanzibar to register children for immunizations before they are born, to ensure all children are vaccinated on time. Children are currently registered when they are already around four weeks old and only at health facilities, which excludes a lot of children born at home. They will build on their existing program in Zanzibar to develop the mobile phone technology used by Community Health Volunteers, who engage with pregnant women in their homes, for registering infants in the third trimester, generating immunization plans, and providing a support tool to educate mothers on the importance of timely vaccinations. They will test their application in the field by recruiting 100 health volunteers and evaluating immunization levels and timing in around 500 infants.

Christoph Nann, Alex Schill, Maik Kaehler and a team from Serviceplan in Germany will test a simple and modern method for generating donations to developing countries. They will use location-based network applications such as Foursquare, which has over 25 million users who record their locations in cafés, shops and restaurants. By setting up collaborations with local retail partners in Germany, they will label their stores on Foursquare with charity projects in developing countries, such as building water pumps, to promote visitors to the stores. Once an organization has been found that can handle the donations, they will launch the locations on a website. When a Foursquare user visits one of the project-labeled stores it will trigger an automatic donation of an agreed amount from the store to that project. The aim is to spread the approach to other cities.

Mustafa NaseemUniversity of MichiganAnn Arbor, Michigan, United States

Grand Challenges Explorations

Immunization Delivery

1 May 2019

Mustafa Naseem of the University of Michigan in the U.S. will create an android application to present digital immunization and performance data from front-line health workers to their medical supervisors to improve vaccination coverage in Pakistan. Polio is a vaccine-preventable disease, eradicated in much of the world yet endemic in Pakistan due to poor compliance with immunization schedules. Vaccine administration in rural provinces is challenging because of understaffed, understocked, and sparsely-located healthcare centers. To improve this, the government introduced eVaccs – a smartphone-based monitoring system to track the movements and vaccinations administered by each vaccinator. However, these data remain largely inaccessible to their direct supervisors. To address this, they will develop an application to present them with relevant data in a useful format in real time. This will enable supervisors to better monitor performance, identify key challenges to comprehensive vaccination coverage, and help them better manage vaccine supplies. They will perform behavioral experiments in the field to test whether their approach positively influences vaccination coverage.

Rachel Teitelbaum of Hervana, Ltd. in Israel will develop and test a biological vaginal formulation that produces a sperm-binding agent, which interferes with sperm motility or fertilization or both. It is hoped that this non-hormonal contraceptive will need only infrequent administration to maintain its effectiveness. In this project's Phase I research, Teitelbaum developed a lead formulation and demonstrated initial proof-of-principle that such an approach can provide effective contraception. In Phase II, Teitelbaum and her team will expand upon this proof-of-principle in animal models to arrive at a long-acting, safe, and effective contraceptive that is ready for evaluation in human trials.

Peter Ngure of Daystar University in Kenya seeks to develop a biological control for sandflies using fungi found in the local soil in Kenya. These entomopathogenic fungi, which attach like parasites onto adult insects and larvae and kill them, will be harvested and cultured to isolate virulent strains that can eradicate sandflies, which are responsible for the spread of visceral leishmaniasis.

David HerrinThe University of Texas at AustinAustin, Texas, United States

Grand Challenges Explorations

Infectious Diseases

1 Nov 2010

David Herrin and colleagues at the University of Texas propose to develop a green-algal food source for mosquito larvae into a biological control agent by engineering their chloroplasts to produce larvacidal proteins. The chloroplast genome has significant advantages for genetic modification, including stability and containment.

Aurelien ForgetUniversity of South AustraliaAdelaide,, South Australia, Australia

Grand Challenges Explorations

Contraceptive Discovery

14 Jun 2017

Aurelien Forget of the University of South Australia in Australia will develop a three-dimensional bioprinted model of the fallopian tube (oviduct) as a screening platform to identify compounds that specifically block sperm activation for developing a female contraceptive that targets male sperm. This contraceptive could in principle be taken before or after intercourse, and would pose no risk to male fertility as it is taken by the female, or to female fertility as it targets a male-specific process. It should also avoid the side effects associated with classical hormonal contraceptives. Sperm first need to be activated (capacitated) in the oviduct before they have the ability to penetrate the cells and protein layer surrounding the egg in order to fertilize it. To reproduce this process in vitro, they will isolate oviduct cell populations from mice and use their synthetic, printable extracellular matrix to build a three-dimensional oviduct that reproduces the four-layered structure. They will assess cell viability and function in their assembled oviduct, as well as its ability to capacitate mouse and human sperm.

Agnes MindilaJomo Kenyatta University of Agriculture and TechnologyNairobi, Kenya

Grand Challenges Explorations

Health Supply Chains

1 Nov 2017

Agnes Mindila of the Jomo Kenyatta University of Agriculture and Technology in Kenya will develop a software application along with blockchain technology to monitor the supply chains delivering vaccines from the producers to the health workers to ensure good quality vaccines are available when needed. They will use blockchain technology, which involves digitally storing information in blocks that are shared across a network of computers and can be continually updated. They will also develop and test a software application so that everyone in the supply chain can access and record information about a specific vaccine to improve transparency and ensure the vaccine is authentic.

Roice Fulton of the Denominator Group in Switzerland will test the value of blockchain, which is a decentralized secure database, for stakeholders such as distributors and health workers to record and monitor the movement of a vaccine along a supply chain, to ensure the availability of sufficient levels of working vaccines. Following the route of a vaccine from the producer to the patient would ensure its safety and allow for better monitoring of stock and supply chain performance, which would improve vaccine availability and help identify ways to increase efficiency and lower costs. Blockchain is an efficient and secure way to share information. They will test their approach in Tanzania, which has a fairly robust supply chain, by tailoring blockchain to integrate with existing platforms, and evaluate its ability to reliably monitor vaccines.

Christine Hrycyna and Jean Chmielewski of Purdue University in the U.S. will develop novel dimeric drugs designed to block a key protein in the malaria parasite that limits the accumulation of anti-malarials in the parasite's digestive system. By inhibiting this protein, this new therapy could eliminate drug resistance in malaria parasites.

Nnaemeka Ikegwuonu of the Smallholders Foundation in Nigeria will improve his Box-in-a-Truck design for extending the lifespan of cassava, which is a major staple food grown by women smallholder farmers, to decrease labor costs associated with cassava processing. Cassava spoils within 24 hours of harvesting, and the traditional method of prolonging life by leaving the crops longer in the ground reduces the nutritional content. He has designed a small, manually transportable truck containing a wire box that is surrounded by moist sawdust and can hold 145 pieces of cassava. This Box in a Truck is inexpensive and can be locally manufactured and maintained. Initial tests showed that cassava stored in this way lasted the duration of the 16 day study period and retained more nutrients than when it is left in the ground. He will test extended time spans and optimize parameters for use, and then field-test the device for its capacity to save labor and its suitability for local conditions across different seasons using 200 women smallholder farmers.

Carmen Gracinda Silvan Scochi from the Universidade de São Paulo in Brazil will encourage mothers of preterm infants in Brazil to exclusively breastfeed them for the first six months to better protect them against infections and optimize their growth and neurodevelopment. The incidence of preterm births in Brazil is increasing, and causes multiple short and long-term complications. Exclusive breastfeeding can limit some of these complications but is particularly challenging with preterm infants due to their incomplete development and the need for hospitalization, as well as there being practical and emotional difficulties for the mother. The existing WHO/UNICEF global program for promoting exclusive breastfeeding has been adapted specifically for preterm infants and involves better educating medical staff so that they provide the practical and emotional support to encourage exclusive breastfeeding. They will establish the program in 10 hospitals/maternity units across Brazil and evaluate its effect on the numbers of preterm infants being exclusively breastfed.

Ricardo Valladares of Siolta Therapeutics in the U.S. will develop a low-cost method to manufacture large quantities of mixed populations of bacteria for use as biotherapeutics to restore a healthy population of gut microbes in infants. A diverse population of bacteria in the infant gut is essential for health, but malnourishment and antibiotics can destroy microbial diversity and cause metabolic and immune problems. Gut health may be restored by treatment with a consortium of bacterial strains. However, mass production of these strains is challenging as many have complex nutritional and environmental growth requirements. To date consortium microbes have been cultured individually, resulting in a costly, small-scale process. They will first study bacterial populations in healthy infant guts to determine what species are required and the combinations that co-exist naturally. To support their growth in vitro, they will optimize a vegetable-based culture media composed of low-cost, widely available food staples, and then apply bioreactor technology used by commercial breweries to manufacture large quantities of the microbial mixture at low cost. Together, these approaches could help make microbiota-based biotherapeutics accessible in low- and middle-income countries.

Wayan VotaDevelopment Gateway, Inc.Washington, District of Columbia, United States

Grand Challenges Explorations

Data Systems

15 Oct 2013

Wayan Vota of Development Gateway in the U.S. will combine data generated by citizens and governments into an interactive interface that can be easily accessed and used by average citizens in order to improve their communities. They will focus on education in three Nairobi slums, and engage the local community and government. An application interface will be designed using relevant datasets, such as school performance statistics, community reports, and geographic data, and used to build an interface that can be accessed over the internet or distributed in print form or via messages sent to mobile phones. They will conduct local workshops to test their approach.

William Kunin of the University of Leeds in the United Kingdom will develop methods to monitor agricultural pest outbreaks in Africa using data from dual-polarization weather radar. Pest infestation is responsible for up to 50% of pre-harvest crop loss in Central Africa, and control depends on the ability to monitor local pest outbreaks and movement over large areas – a difficult and expensive task. Sophisticated dual polarization Doppler weather radar is designed to detect airborne objects like rain and hail. However, because it is sensitive to size and shape, it can also be used to detect specific types of insects, including crop pests, and algorithms exist to separate the different signals. They will use micro-CT scans to create three-dimensional models of pests common to Rwandan crops and conduct simulations to predict radar data patterns for swarms of particular pests at varying densities. Through collaboration with the Rwandan meteorological service, they will analyze radar data to identify pest outbreaks and their movements across the country. Once established, the methods will be applied across Africa to provide a low-cost, advanced warning system for crop protection.

Pushpa Singh of the Civil Society Information Services India in India will develop a common repository to receive, validate, and store information from multiple sources on not-for-profit organizations to make it easier to access support from philanthropic intermediaries. Philanthropic intermediaries currently perform independent searches to find appropriate NGO partners to support, which costs time, money, and effort. The relevant data generated during these searches would benefit others, but it is often wasted, made inaccessible, or in a form that makes it incompatible with similar datasets. To address this, Singh will build a validated, searchable, and up-to-date NGO information source. Using test partners, Singh will design and develop the architecture for the system, which includes a tool that can transform diverse types of data into a standard format and vice-versa, and an tool for importing and export data.

Beth Kolko of the University of Washington in the U.S. will build on recent research that has revealed that current portable ultrasound devices are often too complex for rural midwives in developing countries to use, and will develop instead a streamlined, inexpensive device with limited functionality, a simplified user interface, and a contextual help system. The prototype will be field tested with midwives in Uganda.

Jhpiego proposes a capacity building and sustaining "Day of Birth" approach to bring lifesaving services to remote health facilities where complications must be prevented and managed simultaneously and swiftly, often by a single provider. This approach uses evidence-based practices in prevention and treatment of the two biggest killers of women and newborns in the hours after birth -PPH and neonatal asphyxia. Our approach will increase the knowledge and skills of frontline health workers, and therefore reduce newborn mortality and PPH in the areas where the intervention is applied through: 1) capacity building of facility teams through targeted training in "Helping Babies Breathe" and "Bleeding After Birth," 2) use of a low-cost, easy to use and durable simulator during training and low-dose high-frequency routine practice sessions carried out at the facilities after training, 3) further reinforcement through supportive supervision via phone and text messages, and 4) awareness creation within the community of improved services at the health facilities to boost desire for facility birth.

Suparna Kalghatgi of Bempu Health Private Limited in India will introduce an online, personalized messaging platform to educate parents and caregivers on immunization and address their concerns to increase vaccine compliance and decrease childhood morbidity in India. Despite the existence of a universal immunization program, there are 7.4 million unvaccinated children in India, and only 65% of infants are fully vaccinated by age one. Limited caregiver knowledge is a key barrier to vaccination: parents must understand why vaccination is important and know the prescribed immunization schedule and where vaccine services are available. They will develop BabyOnTrack - an online support system that runs through WhatsApp, a free online messaging application widely used across India, to provide daily communications including practical infant health education, personalized counseling, and vaccination reminders, to new parents. They will test their approach by running small pilots in private and government hospitals where babies will be enrolled as they are discharged after birth and evaluate its effect on parent engagement and vaccination compliance. The program will also help health centers better manage vaccine supplies to reduce waiting times, which will further improve the vaccination experience for caregivers.

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